Erythrocyte glutathione transferase: a new biomarker for hemodialysis adequacy, overcoming the Kt/V(urea) dogma?

Kt/V(urea) ratio is commonly used to assess the delivered dose of dialysis in maintenance hemodialysis (MHD) patients. This parameter only reflects the efficacy of dialytic treatments in removing small toxins, but not middle and protein-bound toxins. Erythrocyte glutathione transferase (e-GST), an enzyme devoted to cell depuration against a lot of large and small toxins, is overexpressed in uremic patients. Aim of the present study is to verify whether e-GST may represent a novel biomarker to assess the adequacy of different dialytic techniques complementary to Kt/V(urea) parameter. Furthermore, it will be investigated whether e-GST could reflect the 'average' adequacy of multiple dialytic sessions and not of a single one treatment as it occurs for Kt/V(urea). One hundred and three MHD patients and 82 healthy subjects were tested. Fourty four patients were treated with standard bicarbonate hemodialysis (HD) and 59 patients were on online hemodiafiltration (HDF). In all MHD patients e-GST activity was 60% higher than in healthy controls. In HDF, e-GST activity was lower than in HD subgroup (8.2±0.4 versus 10.0±0.4 U/g(Hb), respectively). Single-pool Kt/V(urea) and total weekly Kt/V(urea) were higher in HDF than in HD, but no correlation was found between e-GST activity and Kt/V(urea) data. e-GST, whose level is stable during the erythrocyte life-span, provides information on the long-term depurative efficacy of dialysis treatments.

Rheopheresis in vascular diseases.

BACKGROUND: Endothelial dysfunction is a common condition in many microvascular diseases, such as Age-related Macular Degeneration (AMD) and Peripheral Arterial Occlusive Disease (PAOD). Rheopheresis therapy improves ematic viscosity, shear stress and endothelial function while decreasing fibrinogen, LDL-cholesterol and alpha-2-macroglobulin levels. OBJECTIVE: To evaluate the therapeutic efficacy of rheopheresis in patients with microcirculatory diseases. MATERIALS AND METHODS: Eight patients (7 male and 1 female) were treated with rheopheresis: 3 males were affected by AMD, 4 male and 1 female by uremia and PAOD. We used Membrane Differential Filtration (MDF) with an ethinylvinyl alcohol copolymer membrane as plasmafiltrator. Patients with AMD were treated once a week for ten weeks. Patients affected with PAOD were treated twice weekly for 3 weeks and then were placed on a once-a-week program. RESULTS: In all treated patients with AMD, visual acuity improved. In all patients affected with PAOD, we observed a complete resolution of pain; 3 out of 5 had a complete remission of ulcers. There was partial reduction of ulcers in the other patients and no adverse effects were observed. CONCLUSION: Rheopheresis is a safe, effective form of hemorheotherapy.

Successful pregnancy in a uremic patient treated with single needle hemodialysis.

BACKGROUND: Pregnancy is uncommon in patients on maintenance hemodialysis (HD) and it carries a high risk of fetal and maternal complications. Several reports have shown that application of an intensive dialysis regimen is associated with improved infant survival and better clinical conditions of the mother. METHODS: We report the case of a 35-year-old black woman with a prosthesic cardiac valve who was treated daily with single needle HD because of difficult vascular access. RESULT: A healthy full-term female infant with a normal birth weight was electively delivered at 37 weeks. We did not register any complications during or after pregnancy. CONCLUSION: In our experience, single needle HD is able to provide the patient with adequate depuration during pregnancy, the delivery of a full-term healthy infant, and preservation of the arterial-venous fistula from twice-daily vein puncture.

[Selective adsorption of homocysteine using HFR-on line technique]. / Estrazione di omocisteina in corso di HFR on-line.

Homocysteine (Hcy) is grossly elevated in hemodialysis (HD) patients. Treatment with folic acid and/or vitamin B12 fails to normalize Hcy levels in the majority of patients. Treatment with various dialyzers with different flux characteristics has produced contrasting results. Hemodiafiltration reinfusion (HFR) on-line (double chamber hemodiafiltration (HDF) with regenerated ultrafiltrate reinfusion) is a novel method combining the processes of diffusion, convection and absorbance. The ultrafiltrate is regenerated through a charcoal-resin device. Our aim was to observe the effect of the HFR on-line technique on removing Hcy. We investigated the effect of this treatment on Hcy levels in 10 patients with a mean Hcy level of 57.6 micromol/L (range 24.1-119.7). We measured Hcy, folate and vitamin B12 pre- and post-dialysis and in the ultrafiltrate pre- and post-cartridge at 10, 120 and 240 min. Mean Hcy levels were 57.6 and 35.3 micromol/L (range 9.9-80.3) (p=0.005) pre- and post-dialysis, respectively, while folate and vitamin B12 were unchanged. Pre- and post-cartridge Hcy levels were 11.6 vs 2.5 (p=0.005), 9.3 vs 3.9 (p=0.005), 7.7 vs 4.6 micromol/L (p=0.012) at three time points considered, while folate and vitamin B12 were essentially undetectable. These preliminary data, which need confirmation in a long-term study, seem to indicate that HFR on-line reduces Hcy levels, not only through a possible reduction in uremic toxins, but also through the actual removal of Hcy by absorbance on the charcoal-resin cartridge.

Urinary composition and lithogenic risk in normal subjects following oligomineral versus bicarbonate-alkaline high calcium mineral water intake.

OBJECTIVE: A normal dietary calcium intake to reduce intestinal oxalate absorption is essential to avoid recurrence of calcium oxalate stone formation. It is also important in the prevention of osteopenia in idiopathic hypercalciuria. The calcium content of waters used for hydration may vary from very low to relatively high and is an important factor in prevention or additional risk of stone formation. Therefore, the effect of drinking mineral waters of different calcium concentrations on lithogenic risk factors was studied in normal volunteers. MATERIALS AND METHODS: Normal subjects were divided into two groups of 11 and 10 individuals each. All followed a prescribed diet with an average calcium content of 800 mg/day. The water intake for hydration consisted of 2 liters of an oligomineral water with a low calcium content, <20 mg/l (group A) or of a bicarbonate alkaline water with a high calcium content, 370 mg/l (group B). RESULTS: Diuresis increased similarly in both groups; urine calcium increased by about 80 mg/day in group B. A rise in urine oxalate was observed in both groups, along with the increased urine volume. Osmolar excretion increased in group B; urine osmolality decreased significantly only in group A. In spite of the increase in calciuria in group B, Ca/citrate ratio was constant, due to an increase in citrate excretion. Inter-group differences in terms of activity products of calcium phosphate, calculated according with Tiselius's methods, were found. The differences in AP(CaP) index 1 and AP(CaP) index 2 were significant, with higher values in group B, who drank the bicarbonate alkaline mineral water. CONCLUSIONS: Increased water intake between meals to prevent renal stone recurrence should preferably be achieved with a relatively low calcium water and calcium-rich mineral waters should be avoided.

Histomorphometric assessment of bone turnover in uraemic patients: comparison between activation frequency and bone formation rate.

AIMS: The histomorphometric assessment of bone formation rate (BFR/BS) in bone biopsies from uraemic patients is of crucial importance in differentiating low from high turnover types of renal osteodystrophy. However, since BFR/BS relies on osteoblasts, activation frequency (Ac.f), encompassing all remodelling phases, has recently been preferred to BFR/BS. This study was carried out to consider whether estimation of Ac.f is superior, in practical terms, to that of BFR/BS in distinguishing between different rates of bone turnover in uraemic patients. METHODS AND RESULTS: Bone biopsies from 27 patients in predialysis (20 men and seven women; mean age 53 +/- 12 years) and 37 in haemodialysis (22 men and 15 women; mean age 53 +/- 12 years) were examined. The types of renal osteodystrophy were classified on the basis of morphology. Bone formation rate and Ac.f were evaluated according to standardized procedures. The Ac.f was calculated both as a ratio between BFR/BS and wall thickness (W.Th) and as a reciprocal of erosion, formation and quiescent periods (EP, FP and QP). Patients were affected by renal osteodystrophy with predominant hyperparathyroidism (two predialysis and 16 dialysis), predominant osteomalacia (three predialysis and seven dialysis) or that of advanced (nine predialysis and five dialysis) or mild (seven predialysis and four dialysis) mixed type or adynamic type (six predialysis and five dialysis). Activation frequency, which with either formula requires the measurement of W.Th, i.e. the thickness of bone structural units (BSUs), was not calculated in three dialysis patients with severe hyperparathyroidism and in one predialysis and four dialysis patients with severe osteomalacia, because only incomplete BSUs were found. In dialysis, EP was higher in the adynamic than in the other types of osteodystrophy. During both predialysis and dialysis, FP was higher in osteomalacia than in the other forms of osteodystrophy, and in adynamic osteopathy than in hyperparathyroidism or in advanced and mild mixed osteodystrophy. During predialysis and dialysis, QP was higher in the adynamic than in the other forms of osteodystrophy. Correlations were found between BFR/BS and Ac.f, during predialysis (r=0.97) and dialysis (r=0.95). CONCLUSIONS: The superiority of Ac.f in assessing bone turnover, in comparison to BFR/BS, is conceptual rather than practical. The highest values for FP in osteomalacia and for QP in adynamic bone allow a clearer characterization of these low turnover conditions.

Parathyroidectomy in chronic renal failure: short- and long-term results on parathyroid function, blood pressure and anemia.

To evaluate the long-term results of parathyroidectomy (PTX) on parathyroid function, blood pressure and anemia, data of 45 patients with secondary Hyperparathyroidism in dialysis who had undergone PTX were collected retrospectively from 8 different dialysis units. The patients, 25 M and 20 F, mean age 56 +/- 11 years, who were followed up for an average period of 3.3 +/- 2.3 years, were divided into four groups according to the surgical procedure: 19 patients had had a subtotal PTX; 10 patients had undergone total PTX with autotransplantation (AT); 10 patients had had total PTX without AT, and 6 patients had undergone partial PTX. Taking a reduction in intact PTH > 50% as sign of successful PTX, only 5 patients did not attain this result. Considering values of PTH between 20 and 200 pg/ml at the mid-term observation (1-2 years) as the optimal result, values under 20 pg/ml as an expression of permanent hypoparathyroidism, and those above 200 pg/ml as indicating persistent/recurrent hyperparathyroidism, 65.5% of patients operated with subtotal PTX and total PTX + AT had a therapeutic success, versus 31.2% of patients in the other two groups, due to excess permanent hypoparathyroidism and persistent/recurrent hyperparathyroidism; 20 of 45 patients with preoperative hypertension experienced a statistically and clinically significant decrease in blood pressure levels. An increase in serum hemoglobin was also observed, despite a reduction of administered erythropoietin. In conclusion, the results of PTX obtained from this multicenter study are comparable to those reported by single leading centers. Recommended surgical procedures are subtotal PTX and total PTX with AT. The fall in blood pressure in hypertensive patients is clinically significant, and improvement in anemia is also observed with a reduction in erythropoietin dosage.

[Primary non-Hodgkin's lymphoma of the intestine associated with asymptomatic celiac disease in adults]. / Linfoma non-Hodgkin primitivo dell'intestino associato a malattia celiaca asintomatica dell'adulto.

Celiac disease (CD), a gluten-induced enteropathy, is characterized by typical intestinal involvement with classical clinic features in childhood and less frequent features in adult patients. Recognizing pauci- and asymptomatic patients is a critical point in the clinical management of CD because of the high mortality associated with the onset of complications. Among these, malignant diseases are the most severe, particularly squamous cell carcinoma and lymphoma, the latter accounting for 50% of all malignancies occurring in CD patients. The authors describe a 57 years old patient with CD and Enteropathy-Associated-T-Cell Lymphoma, who had no intestinal symptoms but only severe pruritus and hypereosinophilia.